Abstract
Delta-9 desaturases, also known as stearoyl-CoA desaturases, are lipogenic enzymes responsible for the generation of vital components of membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, and gene expression studies of strains carrying mutations in nhr-80 and in the three genes encoding delta-9 desaturases, fat-5, fat-6, and fat-7. The delta-9 desaturase single mutants display only subtle changes in fatty acid composition and no other visible phenotypes, yet the fat-5;fat-6;fat-7 triple mutant is lethal, revealing that endogenous production of monounsaturated fatty acids is essential for survival. In the absence of FAT-6 or FAT-7, the expression of the remaining desaturases increases, and this ability to compensate depends on NHR-80. We conclude that, like mammals, C. elegans requires adequate synthesis of unsaturated fatty acids and maintains complex regulation of the delta-9 desaturases to achieve optimal fatty acid composition.
Highlights
Monounsaturated fatty acids (MUFAs) are key components of membrane phospholipids and triglycerides that play important roles in diverse cellular processes such as membrane function, energy storage, and signaling
SCD1 is important for adult energy metabolism and lipid synthesis [7], while SCD2 is involved in lipid synthesis during embryonic development [8]
This induction depends on nuclear hormone receptor (NHR)-80, a novel NHR that we have identified as a regulator of desaturase expression
Summary
Monounsaturated fatty acids (MUFAs) are key components of membrane phospholipids and triglycerides that play important roles in diverse cellular processes such as membrane function, energy storage, and signaling. Similar to the nhr-80 mutants, the nhr-49 mutants exhibited an increased level of 18:0 accumulation and a decrease in expression of the D9 fatty acid desaturase genes by QPCR with fat-5 and fat-7 as the most reduced [24]. This is consistent with the normal level of fat storage seen in the nhr-80 mutants Though both NHR-49 and NHR80 are required for D9 desaturase expression, their effects on fatty acid metabolism in C. elegans are not identical; NHR-49 appears to regulate a wider range of lipid homeostasis pathways. Because the fat-7 loss-of-function mutant is wild type for fatty acid composition and lifespan it must be concluded that fat-7(RNAi) is having off-target effects on the worm
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